The long-range objective of this Project is to examine neural processing of complex sounds and to uncover the biological correlates of presbycusis, the difficulty in understanding speech in poor listening conditions that develops with advancing age. In everyday listening environments, the elderly have the greatest difficulty understanding speech when the background noise and the speech signal are competing for similar spectral and temporal processing neural channels, as in the case for speech in social situations. A central component in all the proposed experiments is the increasing acoustic complexity of the background noise in order to more closely simulate natural listening conditions of the presbycusic listener. We will measure single unit responses and near-field potentials from the auditory midbrain of young adult, middle-aged and old CBA mice, and on temporal acuity as affected by two types of variables, namely, age-related alterations in auditory midbrain neuropharmacology and age-related deficits in spatial hearing. The first set of experiments test the hypothesis that modifying the action of neurotransmitters critical to auditory function and known to change with age will result in temporal processing deficits in complex spatial listening environments as measured by gap encoding in the inferior colliculus (IC). We will test the effects of chronic blockade of GABA circuits in the IC, and on acute blockade of serotonin receptors using microiontophoresis. The third hypothesis involves both binaural and temporal processing in quiet and background noise and predicts and predicts that the neural substrates of binaural gap temporal encoding of periodic amplitude modulation (AM) are linked to voltage gated potassium channels that are heavily represented in the auditory brainstem. On both theoretical and empirical grounds and consistent with our pilot data, we assert that they will be involved in neural synchrony and fast spiking, important mechanisms for encoding AM. We will test this prediction using electrophysiological measures from mice which lack these channels who should show deficits in temporal coding at high AM rates that correspond to those observed in the aged IC. We envision that the proposed studies will provide new insights into the neural deficits associated with presbycusis, eventually leading to effective interventions or treatments.